Data recently obtained in our laboratory strongly suggest that the left ventricular mechanoreceptors play an important role in the control of the circulation, e.g., in the reflex regulation of the systemic peripheral resistance, especially during exercise and in the monitoring and regulation of left ventricular myocardial contractility. The proposed studies are intended to: (a) Accurately delineate the neural pathway of the reflex initiated by the left ventricular mechanoreceptors under as physiological conditions as possible. (b) Elucidate, at the cellular level, the basic mechanisms underlying the initiation of the Bezold reflex in order to demonstrate conclusively that, since the initiation of this reflex like that of the left ventricular mechanoreceptor reflex is mediated by an increase in left ventricular myocardial contractility, the Bezold reflex is really the left ventricular mechanoreceptor reflex initiated by the veratrum alkaloids. (c) Compare the underlying cellular mechanisms by which the digitalis glycosides and the veratrum alkaloids initiate the left ventricular mechanoreceptor reflex and to determine what role this reflex may play in the therapeutic action of the digitalis glycosides. (d) To interrupt the left ventricular mechanoreceptor reflex loop in conscious, "instrumented" dogs during exercise as well as during the "anticipatory phase" in order to document the feedback changes in myocardial contractility which we anticipate and which we believe to be controlled by this reflex. (e) Finally, by means of selective denervation studies, to demonstrate conclusively the important role played by the strategically located left ventricular mechanoreceptors both in the control of the peripheral resistance and in the control of left ventricular myocardial contractility.